Systems and methods for the treatment of bladder dysfunctions using neuromodulation

ABSTRACT

Systems and Methods treat bladder dysfunctions using neuromodulation stimulation. Bladder emptying through stimulation of urethral afferents, and continence through stimulation of the dorsal genital nerve, is provided with one or more implanted pulse generators and one or more leads. A simple surgical procedure preserves all existing functions. A stimulating catheter is provided to be used as a clinical screening tool. The stimulating catheter is used to measure bladder pressures and stimulate the urethra at the same time.

RELATED APPLICATION

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/931,263, filed May 22, 2007, and entitled“Systems and Methods for the Treatment of Bladder Dysfunctions UsingNeuromodulation Stimulation” which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under grant number1RNS055393-01 awarded by the National Institutes of Health, through theNational Institute of Neurological Disorders and Stroke. The Governmentmay have certain rights in the invention.

FIELD OF THE INVENTION

This invention relates to systems and methods for stimulating nervesand/or muscles in animals, including humans, to treat bladderdysfunctions.

BACKGROUND OF THE INVENTION I. Neuromodulation Stimulation

Neuromodulation stimulation (the electrical excitation of nerves toindirectly affect the stability or performance of a physiologicalsystem) can provide functional and/or therapeutic outcomes. Whileexisting systems and methods can provide remarkable benefits toindividuals able to be treated with neuromodulation stimulation, manylimitations and issues still remain. For example, existing systems canoften require the user to wear an external stimulator, which may providea positive functional outcome, but may also negatively affect quality oflife issues.

A variety of products and treatment methods are available forneuromodulation stimulation, including external and surgically implantedstimulators. As an example, neuromodulation stimulation has been usedfor the treatment of lower urinary tract dysfunctions, including bladderdysfunctions, which affects both men and women. In addition, a wide,range of other options exist for the restoration of bladder function.Treatments include everything from medications, devices such ascatheters, and psychological counseling.

Both external and implantable devices are available for the purpose ofneuromodulation stimulation for the restoration of bladder function. Theoperation of these devices typically includes the use of an electrodeplaced either on the external surface of the skin or a surgicallyimplanted electrode. Although these modalities have shown the ability toprovide a neuromodulation stimulation with some positive effects, theyhave received limited acceptance by patients because of theirlimitations of portability, limitations of treatment regimes, andlimitations of ease of use and user control.

II. Bladder Function

In a healthy person, the lower urinary tract provides two functions:storage of urine (continence) and urination (micturition). Duringcontinence, the bladder is relaxed and fills with urine while thesphincter contracts to prevent leakage of urine. During micturition, thesphincter relaxes and the bladder contracts to expel urine through theurethra. Flow receptors along the urethra detect this flow of urine andsend afferent (sensory) signals to the sacral spinal cord, whichaugments urination by decreasing (−) sphincter tone and increasing (+)efferent (motor) drive to the bladder detrusor muscle (see FIG. 1). Thispositive feedback continues until the urethral flow receptors no longerdetect fluid flow and stop sending afferent signals to the spinal cord,resulting in relaxation of the bladder and the beginning of the nextcontinence phase.

Continence may be restored through electrical stimulation of the dorsalgenital nerve, which is a branch of the pudendal nerve. Similarly,micturition may be restored through electrical stimulation of urethraafferent nerves, which are also branches of the pudendal nerve (seeFIGS. 2 and 3). Electrical stimulation of the urethral afferents candrive this positive feedback and activate the micturition circuitry inthe sacral spinal cord, just as if the person was already in the processof urination. Just as in micturition in a healthy person, the sacralspinal cord would coordinate the process of urination by relaxing thesphincter and contracting the bladder to expel urine. This method hasbeen used to empty the bladder in cats before and after spinaltransection at T12 and achieve bladder contraction in humans after suprasacral spinal cord injury (SCI).

The conditions needed to evoke bladder emptying via activation ofurethral afferents are known and include bladder volume, stimulationfrequency, and neural circuitry. The bladder must contain more than aminimum threshold volume to initiate the micturition-like response, andthe threshold volume varies markedly from individual to individual buton average is approximately 33 percent less than the volume at which thefirst distention-evoked contractions occur. Stimulation of the urethralafferents with frequencies between 1 and 50 Hz has been shown to evokemicturition-like responses in decerebrate and anesthetized animals. 33Hz has been shown to be the stimulation frequency most effective inevoking sustained bladder contractions and voiding in cats, andstimulation frequencies of 20 to 40 Hz appear to be the most effectivein eliciting micturition-like bladder contractions in persons with SCI.Furthermore, this frequency range has been shown to be identical tofrequencies at which urethral afferents fire during urethral flow.

Stimulating urethral afferents at the appropriate frequency may evoke amicturition-like reflex if the starting bladder volume is abovethreshold. Electrical stimulation of urethral afferents may evokemicturition even if some of the neural circuitry is damaged orcompromised (e.g., through disease or injury, including spinal cordinjury). However, stimulation is more likely to be successful if thesacral spinal cord is intact because anatomical mapping andelectrophysiology studies show that the sacral cord contains the spinalmicturition circuitry. This is supported by observations of coordinatedbladder-sphincter activity in humans with supra sacral injuries andconfirmed by coordinated micturition-like activity evoked by electricalstimulation of urethra afferents before and after spinal transection(T10-T12) in cats.

III. Present Treatment Methods

The inability to empty the bladder is a significant problem that is notadequately addressed by present treatment options. Approximately 250,000persons in the United States are living with a spinal cord injury (SCI),with approximately 10,000 more persons being spinal cord injured eachyear, and even more persons have damaged neural circuitry from diseaseor other injuries. In SCI persons, the SCI prevents the brain stem fromcommunicating with the lower urinary tract, eliminating voluntarycontrol of continence (urine storage) and micturition (urineevacuation). Bladder contractions become ineffective in emptying thebladder, leaving a high residual volume. The urinary system transformedby SCI typically results in additional complications such as uretericreflux and obstruction, infection of the kidneys, long-term renaldamage, episodes of autonomic dysreflexia with dangerous rises in bloodpressure, bladder trabeculation, and frequent urinary tract infections.

For a person with SCI, the direct medical costs associated with urinarytract dysfunction may exceed $8,000 each year, making up a substantialcomponent of the estimated $31,000 to $75,000 annual health care andliving expenses of individuals with spinal injury. Furthermore, the lossof control of urinary function alters social relationships and can bepersonally demoralizing, and it can lead to depression, anger, poorself-image, embarrassment, frustration and can prevent persons fromachieving their personal goals.

As previously identified, many techniques have been developed to treatlower urinary tract dysfunction brought about by SCI and otherconditions. Presently, self-catheterization proves to be the bestnon-invasive method to care for lower urinary tract dysfunction, butmany persons with lower urinary tract dysfunction sustain multipleinfections per year, and persons with SCI often lack the physicalability to catheterize themselves. Alternative methods have beendeveloped to empty the bladder by preventing the sphincter from closingthe urethra, but most of them, including sphincterotomy, sphincterparalysis, and urethral stenting, leave the person incontinent and leadto further complications. Other techniques, such as balloon dilation,have a low (e.g., 15 percent) success rate, and presently, no techniquesprovide effective bladder emptying without the secondary consequencesthat limit widespread acceptance among the patient population.

There is a significant market need for providing bladder emptying withelectrical stimulation. As previously stated, an estimated 250,000persons with SCI in the United States suffer from urinary retention atan annual cost of $1.5 billion. VOCARE (FineTech Medical, UK) is theonly commercially available neurostimulation system that providesbladder emptying, but it is used by less than one percent of eligiblepatients. It has been found that few people elect to receive the VOCAREsystem because it requires 1) a time-consuming (e.g., more than eighthours), invasive surgical procedure and 2) an irreversible nervetransection, resulting in the loss of sexual function and reflexdefecation. The systems and methods of the present invention provide analternative approach with several significant advantages over the VOCAREsystem.

The present novel invention addresses the need for a system that issimpler to implant and more acceptable to persons with bladderdysfunctions. Most potential VOCARE patients are unwilling to undergothe extensive surgery and extended inpatient hospital stay, and evenfewer will consider sacrificing sexual function and reflex defecation inexchange for bladder control.

The present novel invention provides systems and methods for bladdercontrol with a simple (e.g., less than two hour) outpatient procedurethat may preserve all existing functions. Implantation of a VOCAREsystem requires the coordination of doctors from multiple disciplines,but the novel approach of the present invention allows the patient'sregular Urologist to implant the system. Presently, it is difficult todetermine how effective a VOCARE system may be prior to implantation. Incomparison, the novel systems and methods include a stimulating catheterelectrode (see FIG. 20A) adapted to be used as a quick (e.g., less than15 minutes), minimally-invasive way to determine how well a patient mayrespond to the system before surgery. The stimulating catheter will bedescribed further in section “V. Stimulating Catheter.” The novelsystems and methods of the present invention combine bladder emptyingthrough stimulation of urethral afferents and continence throughstimulation of the dorsal genital nerve to provide complete bladdercontrol with a simple surgical procedure that preserves all existingfunctions. This innovative approach may also benefit individuals withbrainstem stroke or multiple sclerosis, who often do not have bladdercontrol.

There remains a need for systems and methods that can treat lowerurinary tract dysfunctions as a first line of treatment and for thosewho have not responded to conventional therapies, in a straightforwardmanner, without requiring drug therapy and complicated and irreversiblesurgical procedures.

SUMMARY OF THE INVENTION

The novel systems and methods of the present invention combine bladderemptying through stimulation of urethral afferents and continencethrough stimulation of the dorsal genital nerve to provide completebladder control with a simple surgical procedure that preserves allexisting functions.

Alternatively, at least one or more leads may activate selectivelyeither the urethral afferent pathway to provide micturition or thegenital afferent pathway to provide continence by changing stimulusparameters such as frequency, amplitude, and/or pulse width.

A stimulating catheter is provided to be used as a clinical screeningtool. The stimulating catheter may be used to measure bladder pressuresand stimulate the urethra at the same time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of sensory signals and the spinal circuitryactivity that coordinates efferent and afferent nerve activity andproduces bladder functions.

FIG. 2 is a lateral section view of a male pelvic girdle region.

FIG. 3 is a lateral section view of a female pelvic girdle region.

FIG. 4 is an anterior anatomic view of an exemplary embodiment of asystem after implantation in a pelvic region for restoration of bladderfunctions.

FIGS. 5A and 5B are front and side views of one embodiment of thegeneral purpose implantable pulse generator shown in FIG. 4, which maybe powered by a primary or rechargeable battery.

FIGS. 6A and 6B are front and side views of an alternative embodiment ofthe general purpose implantable pulse generator as shown in FIG. 4,which may be powered by a primary or rechargeable battery.

FIG. 7 is a plane view of the implant system shown in FIG. 4, forrestoration of bladder functions, showing implant depth andnon-inductive wireless telemetry features.

FIGS. 8 and 9 are perspective views of the lead and electrode associatedwith the system shown in FIG. 4.

FIG. 10 is a side interior view of a representative embodiment of a leadof the type shown in FIGS. 8 and 9.

FIG. 11 is an end section view of the lead taken generally along line11-11 in FIG. 10.

FIG. 12 is an elevation view, in section, of a lead and electrode of thetype shown in FIGS. 8 and 9 residing within an introducer sleeve forimplantation in a targeted tissue region, the anchoring members beingshown retracted within the sheath.

FIG. 13 shows an anatomical view of an anterior approach for implantinga lead as part of the system shown in FIG. 4.

FIG. 14 shows a lateral section view of the anterior approach forimplanting a lead, as shown in FIG. 13.

FIG. 15 shows an anatomical view of a perineal approach for implanting alead as part of the system shown in FIG. 4.

FIG. 16 shows a lateral section view of the perineal approach forimplanting a lead, as shown in FIG. 15.

FIG. 17 shows an anatomical view of a posterior approach for implantinga lead as part of the system shown in FIG. 4.

FIG. 18 shows a lateral section view of the posterior approach forimplanting a lead, as shown in FIG. 17.

FIG. 19 is an anatomical view showing the implant system implanted in apelvic region, and a clinical programmer within (or outside) the sterilefield using non-inductive wireless telemetry to communicate with theimplanted pulse generator.

FIG. 20A is a perspective view of a stimulating catheter adapted forurethral stimulation of both males and females.

FIG. 20A is a perspective view of stimulating catheter electrode adaptedfor urethral stimulation of both males and females.

FIG. 20B is a detailed plan view of an electrode secured to the catheterbody of the stimulating catheter shown in FIG. 20A.

FIG. 20C is a perspective view of the stimulating catheter shown in FIG.20A, except with an alternative configuration of electrode placement.

FIG. 21 is a cross-sectional view taken along lines 21-21 of FIG. 20A,showing a two lumen configuration used in conjunction with thestimulating catheter.

FIG. 22 is a cross-sectional view taken along lines 22-22 of FIG. 20A,showing an electrode used in conjunction with the stimulating catheter.

FIG. 23 is a lateral anatomical view showing the stimulating catheter ofFIG. 20A positioned within the urethra of a human male to selectivelystimulate urethral afferents.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention which may be embodied inother specific structures. While the preferred embodiment has beendescribed, the details may be changed without departing from theinvention.

I. Restoration of Bladder Function

The present novel invention provides systems and methods of bladdercontrol to individuals with neurological disorders, including spinalcord injury (SCI), who do not have volitional control over their lowerurinary tract. This lack of control results in incontinence andinability to urinate on demand, which frequently causes many seriousadverse health effects. The only commercially available electricalstimulation product (VOCARE, FineTech Medical, UK) to restore fullbladder control in persons with SCI includes an electrode placed on thesacral spinal motor nerves to empty the bladder. It also requirespermanently severing sacral spinal sensory nerves (rhizotomy) to achievecontinence.

Because this rhizotomy is irreversible and because it may result in lossof sexual function, VOCARE has not been widely accepted among thepotential patient population.

The features and benefits of the present invention provide alternativeneurostimulation systems and methods to restore bladder control thatdoes not require electrode placement on the spinal nerve roots and doesnot require rhizotomy.

The pudendal nerve(s), their branches and/or their roots may bestimulated to restore lower urinary tract functions, including bladderemptying (urination) and/or storage (continence).

Electrical stimulation of the genital nerve(s) can provide continence,and electrical stimulation of the urethral sensory nerve(s) can providemicturition. Both of these pathways (genital and urethral) can, beactivated at multiple locations and/or anatomical levels: at the mostsuperficial level at and/or near the skin and/or urethra; at and/or nearthe respective urethral and/or genital nerve; at and/or near thepudendal nerve; and/or at and/or near the sacral nerve root(s).

Both the caudal and rostral portions of the urethra are innervated byurethral afferents in the cat, and both portions of the urethra arethought to be innervated by urethral afferents in the human (see FIGS. 1to 3). One embodiment of the present invention may include stimulationof the caudal urethra because it contains the majority of the largerlamellated end-organs that act as urethral flow receptors. However, ifstimulation of the caudal urethra is not effective to evoke bladdercontractions, an alternative embodiment of the present invention maystimulate the rostral urethra because it is thought to contain adifferent type of flow receptors also known to evoke micturition-likeresponses in cats and humans after SCI. Or, both caudal and rostralportions of the urethra may be stimulated.

Combinations of lead placement may be used to restore bladder function.At least one or more lead(s) may activate the genital sensory pathway toproduce urine storage (continence). At least one or more lead(s) mayactivate the urethral sensory pathway to provide bladder emptying(micturition). These lead(s) and functions may be combined to providecomplete bladder control (storage and emptying) or used individually toprovide either function (storage or emptying) as needed. Alternatively,at least one or more leads may activate selectively either the urethralafferent pathway to provide micturition or the genital afferent pathwayto provide continence by changing stimulus parameters such as frequency,amplitude, and/or pulse width.

For example, electrical stimulation of pudendal nerve afferentsdifferentially activates continence-like and micturition-like reflexesdependent on the frequency of stimulation. Different groups of pudendalnerve afferents can generate either inhibition or excitation of thebladder. Stimulation of genital and/or anal sensory pathways in thepudendal nerve inhibits the bladder by decreasing parasympatheticoutflow in the pelvic nerve to the bladder detrusor muscle and byincreasing sympathetic outflow in the hypogastric nerve. Bladderinhibition may be evoked by low frequency stimulation (e.g., 2 to 20 Hz)of pudendal nerve afferents; and inhibition may be lost during higherfrequency (e.g., 35 Hz) stimulation.

Excitation of the bladder can be produced by stimulation of urethralsensory pathways over a range of stimulus frequencies. However, higherfrequency (e.g., 20 to 40 Hz) stimulation may be more effective than 10Hz stimulation at evoking bladder contractions, consistent with thefiring rates of urethral afferents in response to urethral fluid flowthat is capable of evoking bladder excitation.

The compound pudendal nerve contains both genital sensory (inhibitory)and urethral sensory (excitatory) pathways. Both excitatory andinhibitory pathways can be accessed at the level of the pudendal nerveand activated differentially according to stimulus frequency. Thus, itmay be possible to control selectively both continence and micturitionwith a single electrode on a peripheral nerve (i.e. the pudendal nerveand/or its branches and/or its roots).

One embodiment of the present invention uses a lead and electrode placedin the pelvic region near pudendal urethral afferents to achieveurination and a lead and electrode placed in the pelvic region near thedorsal genital nerve to achieve continence (see FIG. 4). It is knownthat continence can be achieved with dorsal genital nerve stimulation.This embodiment includes a stimulator and two electrode leads adapted tocombine techniques for bladder emptying and continence.

II. Implant System

An implant system may be used to provide electrical stimulation of atarget nerve A and/or a target nerve B (e.g., the pudendal nerve and/orbranches and/or roots, and/or the dorsal genital nerve, and/or urethralafferents), for the restoration of bladder function on demand and with asimple surgical procedure that preserves the existing anatomy. As usedin this disclosure, it is to be appreciated that at least the terms“nerve”, “lead”, “electrode”, and “IPG” can include both the singular orplural meaning.

The electrical stimulation may be applied, with any type of electricalcontact such as one or more leads having one or more electrodes placedin, on, around, or near any of the target nerves A and/or target nervesB named above. The lead may also include the ability to delivermedications or drugs as an adjunct to electrical stimulation. Note thatthe electrode may be in contact with the target nerve, or it may be somedistance (on the order of centimeters) away because it does not have tobe in contact with the target nerve to activate it.

Stimulation may be applied through a lead/electrode, such as a fine wireelectrode, paddle electrode, intramuscular electrode, or adiposeelectrode, inserted via a needle introducer or surgically implanted inproximity of the target nerve. When proper placement is confirmed, asindicated by patient sensation or visible movement of related organ(s)such as the penis, scrotum, perineal muscle, perineal skin, and/or analsphincter, (or clitoris for women), the needle may be withdrawn, leavingthe electrode in place. Stimulation may also be applied through apenetrating electrode, such as an electrode array comprised of anynumber (e.g., greater than or equal to one) of needle-like electrodesthat are inserted into the target nerve. In both cases, the lead may beplaced using a needle-like introducer, allowing the lead/electrodeplacement to be minimally invasive.

Alternatively, stimulation may be applied through any type of nerve cuff(spiral, helical, cylindrical, book, flat interface nerve electrode(FINE), slowly closing FINE, etc.) that is surgically placed on oraround a target nerve.

In all cases, the lead may exit through the skin and connect with one ormore external stimulators, or the lead(s) may be routed subcutaneouslyto one or more implanted pulse generators (IPG), or they may beconnected as needed to internal and external coils. The IPG may belocated some distance (remote) from the electrode, or the IPG may beintegrated with the electrode, eliminating the need to route the leadsubcutaneously to the IPG.

Control of the stimulator and stimulation parameters may be provided byone or more external controllers. In the case of an external stimulator,the controller may be integrated with the external stimulator. The IPGexternal controller (i.e., clinical programmer) may be a remote unitthat uses non-inductive radio frequency (RF) wireless communication tocontrol the IPG. The external or implantable pulse generator may useregulated voltage (e.g., 10 mV to 20 V), regulated current (e.g., 10 μAto 50 mA), and/or passive charge recovery to generate the stimulationwaveform.

The pulse may by monophasic, biphasic, and/or multi-phasic. In the caseof the biphasic or multi-phasic pulse, the pulse may be symmetrical orasymmetrical. Its shape may be rectangular or exponential or acombination of rectangular and exponential waveforms. The pulse width ofeach phase may range between e.g., 10 μsec and 10 to the sixth powerμsec.

Pulses may be applied in continuous or intermittent trains (i.e., thestimulus frequency changes as a function of time). In the case ofintermittent pulses, the on/off duty cycle of pulses may be symmetricalor asymmetrical, and the duty cycle may be regular and repeatable fromone intermittent burst to the next or the duty cycle of each set ofbursts may vary in a random (or pseudo random) fashion. Varying thestimulus frequency and/or duty cycle may improve and/or optimize theresponse, and assist in preventing fatigue, warding off habituation,lessening the effects of long term potentiation or long termde-potentiation, because of the stimulus modulation.

The stimulating frequency may range from e.g., 1 to 300 Hz, and thefrequency of stimulation may be constant or varying. In the case ofapplying stimulation with varying frequencies, the frequencies may varyin a consistent and repeatable pattern or in a random (or pseudo random)fashion or a combination of repeatable and random patterns that may becycles through.

The stimulation pulses could be applied to a left target nerve and aright target nerve with different parameters, or the stimulation pulsescould be applied to different branches of the same target nerve atdifferent parameters, such as different frequencies, to provide the bestresponse. For example, the left target nerve A could be stimulated at 25Hz, and the right target nerve A could be stimulated at 30 Hz.

By way of an additional non-limiting example, 20 Hz may be used for allstimulation or 10 Hz may be used for target A stimulation and 40 Hz maybe used for target B stimulation, and, target A may be stimulated at 2mA and target B may be stimulated at 0.050 mA or vice versa, or bothtarget A and target B may be stimulated at the same amplitude.

FIG. 4 shows an exemplary embodiment of an implant system 10 for therestoration of bladder function in animals, including humans. It is tobe appreciated that multiple implant system configurations are possible.As non-limiting examples, a single IPG 18 may be coupled to a singlelead 12 to unilaterally stimulate a single target nerve (either A or B);or a single IPG may be coupled to two leads to bilaterally stimulate asingle target nerve (either A or B); or a single IPG may be coupled totwo leads to unilaterally stimulate a target nerve A and target nerve B;or two IPGs may be implanted, each being coupled to a single lead tobilaterally stimulate a single target nerve (either A or B); or two IPGsmay be implanted, each being coupled to a single lead to unilaterallystimulate a target nerve A and target nerve B; or two IPGs may beimplanted, each being coupled to two leads to bilaterally stimulate atarget nerve A and a target nerve B. It is to be appreciated thatadditional system configurations exist.

Referring to FIG. 4, the system 10 includes at least one implantablelead 12 having a proximal end and a distal end, the distal end beingcoupled to an implantable pulse generator or IPG 18. The lead 12 and theimplantable pulse generator 18 are shown implanted within a pelvicregion of a human or animal body, although other implant sites arepossible.

In the embodiment shown, the distal end of the lead 12 includes at leastone electrically conductive surface, which will in shorthand be calledan electrode 16. The electrode 16 may be implanted in electricalconductive contact with at least a target nerve A and/or a target nerveB. The implantable pulse generator 18 includes a connection header 14that desirably carries a plug-in receptacle 15 (connector) for thedistal end of the lead 12 (see FIGS. 5A and 5B). In this way, the leadelectrically connects the electrode 16 to the implantable pulsegenerator 18.

The implantable pulse generator 18 may be sized and configured to beimplanted subcutaneously in tissue, desirably in a subcutaneous pocket,which can be remote from the electrode 16, as FIG. 4 shows. Desirably,the implantable pulse generator 18 may be sized and configured to beimplanted using a minimally invasive surgical procedure.

The lead 12 and electrode 16 are sized and configured to be implantedpercutaneously in tissue, and to be tolerated by an individual duringextended use without pain or discomfort. The comfort is both in terms ofthe individual's sensory perception of the electrical waveforms that theelectrode applies, as well as the individual's sensory perception of thephysical or mechanical presence of the electrode and lead. In the caseof the mechanical presence, the lead 12 and electrode 16 are desirably“imperceptible.”

In particular, the lead 12 and electrode 16 are sized and configured toreside with stability in the lower pelvic region of the body (see FIG.4). It has been discovered that, when properly placed in this region,one or more lead/electrode(s) are uniquely able to deliver electricalstimulation current to a target nerve A and/or a target nerve B to treatbladder dysfunction.

FIGS. 5A and 5B, and 6A and 6B, show multiple embodiments of animplantable pulse generator 18 of the present invention, and will bedescribed in greater detail later. The implantable pulse generator 18includes a circuit 20 that generates electrical stimulation waveforms.An on-board, primary or rechargeable battery 22 desirably provides thepower. The implantable pulse generator 18 also desirably includes anon-board, programmable microcontroller 24, which carries embedded code.The code expresses pre-programmed rules or algorithms under which thedesired electrical stimulation waveforms are generated by the circuit20. The implantable pulse generator 18 may also include an electricallyconductive case 26, which can also serve as the return electrode for thestimulus current introduced by the lead/electrode when operated in amonopolar configuration.

The pulse generator 18 may be sized and configured to be implantedsubcutaneously in tissue at an implant depth of between about fivemillimeters and about twenty millimeters, desirably in a subcutaneouspocket remote from the electrode 16 (see FIG. 7) and using a minimallyinvasive surgical procedure. This implant depth may change due to theparticular application, or the implant depth may change over time basedon physical conditions of the patient. As shown in FIG. 4, theimplantation site can comprise a more medial tissue region in the lowerabdomen. There, the pulse generator 18 can reside for extended usewithout causing pain and/or discomfort and/or without effecting bodyimage. Alternatively, the implantation site can comprise a tissue regionon the posterior hip, for example.

The implant system 10 may include an external patient controller 80 (orcontroller-charger when a rechargeable battery is used). The patientcontroller 80 may be sized and configured to be held or worn by theindividual to transcutaneously activate and deactivate and/or modify theoutput of the pulse generator 18. The patient controller 80 may, e.g.,be a simple magnet that, when placed near the site where the pulsegenerator 18 is implanted, toggles a magnetic switch within theimplantable pulse generator 18 between an on condition and an offcondition, or advances through a sequence of alternative stimulus modespre-programmed by the clinician into the implantable pulse generator 18.

Alternatively, and as can be seen in FIGS. 4 and 7, the patientcontroller 80 may comprise more sophisticated circuitry that would allowthe individual to make these selections through RF (Radio Frequency)wireless telemetry communications (rather that an inductively coupledtelemetry) that passes through the skin and tissue within an arm'slength distance from the implanted pulse generator, e.g., the controller80 may be capable of communicating with the pulse generator 18approximately three to six feet away from the implanted pulse generator(and the pulse generator may be able to communicate with thecontroller).

The wireless telemetry 82 provides reliable, bidirectionalcommunications with a patient controller-charger and a clinicalprogrammer, for example via an RF link in the 402 MHz to 405 MHz MedicalImplant Communications Service (MICS) band per FCC 47 CFR Part 95, orother VHF/UHF low power, unlicensed bands.

With the use of the patient controller 80, the wireless link 82 allows apatient to control certain parameters of the implantable pulse generatorwithin a predefined limited range. The parameters may include theoperating modes/states, increasing/decreasing or optimizing stimuluspatterns, or providing open or closed loop feedback from an external orinternal sensor or control source. The wireless telemetry 82 alsodesirably allows, the user to interrogate the implantable pulsegenerator 18 as to the status of its internal battery 22 (either primaryor rechargeable). The full ranges within these parameters may becontrolled, adjusted, and limited by a clinician, so the user may not beallowed the full range of possible adjustments.

In one embodiment, the patient controller 80 may be sized and configuredto couple to a key chain. It is to be appreciated that the patientcontroller 80 may take on any convenient shape, such as a ring on afinger, or a watch on a wrist, or an attachment to a belt, for example.The patient controller may also use a magnetic switch to enable the userto turn the IPG on/off.

The clinical programmer 52 may be used by a clinician to program thepulse generator 18 with a range of preset stimulus parameters. The usermay then turn the implant system On/Off using the wireless patientcontroller 80. The patient controller 80 may be then programmed by thepulse generator, i.e., the range of or a subset of the preset stimulusparameters previously downloaded by the clinical programmer 52 may beuploaded to the controller 80. This range of preset stimulus parametersallows the user to make adjustments to the stimulus strength within thepreset range. Stimulation may be delivered at a level that may beinitially set at or above the sensory threshold of the user, but is notuncomfortable. The user may get accustomed to the stimulation level, andmay adjust the stimulation up or down within the preset range.

According to its programmed rules, when switched on, the implantablepulse generator 18 generates prescribed stimulation waveforms throughthe lead 12 and to the electrode 16. These waveforms stimulate a targetnerve A and/or a target nerve B in a manner that achieves the desiredphysiologic response.

Using the controller 80, the individual may turn on or turn off thebladder function control waveforms at will or adjust the waveforms toachieve the desired functional restoration result. As previouslydiscussed, bladder function is just one example of a functionalrestoration result. Additional examples of desirable therapeutic(treatment) or functional restoration indications will be described insection “VI. Representative Indications.”

The system 10 desirably includes means for selectively varying thefrequency or range of frequencies for a variable duration at which thestimulation waveforms are applied by the one or more electrodes 16. Bymodulating the frequency and/or duration of the stimulation waveform,the same system components and placement of electrodes can serve toachieve markedly different physiologic responses, and in addition,reduce habituation.

The shape of the pulse waveform can vary as well. It can, e.g., be atypical square pulse, or possess a ramped shape, rectangle, exponential,and/or some combination. The pulse, or the rising or falling edges ofthe pulse, can present various linear, exponential, hyperbolic, orquasi-trapezoidal shapes. The stimulation waveform can be continuous, orit can be variable and change cyclically or in step fashion in magnitudeand waveform over time.

In a non-limiting exemplary embodiment, the stimulus waveforms mayinclude a variable frequency for a variable duration (e.g., a firststimulation at 20 Hz for 2 seconds, then 30 Hz for 3 seconds, then 25 Hzfor 1 second, and so on), intermittent stimulation (apply stimulation inbursts separated by pauses in stimulation (e.g., stimulation for 3seconds, rest for 2 seconds, repeat, and so on). The stimulus waveformsmay also include a continuously or intermittently applied duty cycle ofpulses. This may be considered the same as changing the frequency but italso refers to 1) the duration of bursts of stimulation and 2) theduration of pauses between the bursts. For example, a variable dutycycle for intermittent pulses may include stimulation with 10 pulses,then off for 500 milliseconds, stimulation with 15 pulses, then off for750 milliseconds, stimulation with 5 pulses, then off for 2 seconds, andit could keep going in this variable pattern.

The stimulus waveforms may also include stimulation at differentamplitudes and different frequencies. Thus, amplitude and/or frequencymodulation may be used to control and/or improve the response. Varyingthe amplitude may also provide another form of anti-habituation control,allowing a bladder function (e.g., micturition) to be more complete thanif a target nerve was stimulated at a constant amplitude. Amplitudemodulation may also more realistically recreate the varying level offiber activation that occurs during urination.

The patient controller 80 and/or a clinical programmer 52, for example,may include a manual-actuated switch or control knob which an operatoroperates or tunes to acquire a desired waveform frequency, given thedesired physiologic response.

As previously described, FIG. 4 shows an exemplary embodiment of asystem 10 adapted for the functional restoration of bladder function.The assembly includes at least one implantable lead 12 and electrode 16coupled to at least one implantable pulse generator or IPG 18. The lead12 and the implantable pulse generator 18 are shown implanted within apelvic region of a human or animal body.

Desirably, the components of the implantable pulse generator 18 aresized and configured so that they can accommodate several differentindications, without major change or modification (see FIGS. 5A to 6B).Examples of components that desirably remain unchanged for differentindications include the case 26, the battery 22, the microcontroller 24,much of the software (firmware) of the embedded code, the powermanagement circuitry 40, and the stimulus power supply, both of whichare part of the circuitry 20. Thus, a new indication may require onlychanges to the programming of the microcontroller 24. Most desirably,the particular code may be remotely embedded in the microcontroller 24after final assembly, packaging, and sterilization of the implantablepulse generator 18.

Certain components of the implantable pulse generator 18 may be expectedto change as the indication changes. For example, due to differences inleads and electrodes, the connection header 14 and associatedreceptacle(s) for the lead may be configured differently for differentindications. Other aspects of the circuit 20 may also be modified toaccommodate a different indication; for example, the stimulator outputstage(s), sensor(s) and/or sensor interface circuitry. In addition, thecase size may change due to a different header configuration and/or adesire to increase or decrease the battery size or capacity (compareFIGS. 5A and 5B to 6A and 6B).

In this way, the implantable pulse generator 18 accommodates implantingin diverse tissue regions and also accommodates coupling to at least onelead 12 and an electrode 16 having diverse forms and configurations,again depending upon the therapeutic or functional effects desired. Forthis reason, the implantable pulse generator can be considered to begeneral purpose or “universal.”

The implantable pulse generator 18 may be of the type described inco-pending U.S. patent application Ser. No. 11/517,056, filed Sep. 7,2006, and entitled “Implantable Pulse Generator Systems and Methods forProviding Functional and/or Therapeutic Stimulation of Muscles and/orNerves and/or Central Nervous System Tissue,” which is incorporatedherein by reference. The pulse generator 18 includes a circuit thatgenerates electrical stimulation waveforms. An on-board battery 22(primary or rechargeable) provides the power. The pulse generator 18also includes an on-board, programmable microcontroller 24, whichcarries embedded code. The code expresses pre-programmed rules oralgorithms under which the desired electrical stimulation waveforms aregenerated by the circuit. The small metal case (e.g., titanium and/ortitanium 23) of the pulse generator may also serve as the returnelectrode for the stimulus current introduced by the lead/electrode whenoperated in a monopolar configuration.

The functional elements of the implantable pulse generator 18 (e.g.,circuit 20, the microcontroller 24, the battery 22, and the connectionheader 14) are integrated into a small, composite case 26. Referring toFIGS. 5A and 5B, the case of the pulse generator 18 defines a smallcross section; e.g., desirably about (5 mm to 10 mm thick)×(15 mm to 40mm wide)×(40 mm to 60 mm long), and more desirably about (7 mm to 8 mmthick)×(25 mm to 35 mm wide)×(45 mm to 55 mm long). The pulse generatoralso defines a generally pear-shaped case. The generally pear-shapedcase can be described as including a bottom portion defining a curvedsurface having a radius, inwardly tapering sides, and a top portionbeing generally flat, as shown in FIGS. 5A and 5B. This geometryprovides a case including a larger end (bottom portion) and a smallerend (top portion) and allows the smaller end of the case to be placedinto the skin pocket first, with the larger end being pushed in last.The shape and dimensions of the pulse generator 18 produce a volume ofapproximately seven to nine cubic centimeters, and more desirably abouteight cubic centimeters, and a weight of approximately seventeen grams.

In an alternative embodiment seen in FIGS. 6A and 6B, the case of thepulse generator 18 defines a small cross section; e.g., desirably about(7 mm to 13 mm thick)×(45 mm to 65 mm wide)×(30 mm to 50 mm long), andmore desirably about (9 mm to 11 mm thick)×(50 mm to 60 mm wide)×(35 mmto 45 mm long). The pulse generator also defines a generally oval-shapedcase. The generally oval-shaped case can be described as consistinggenerally of two congruent semicircles and two equal and parallel lines.The shape and dimensions of the pulse generator 18 produce a volume ofapproximately fifteen to nineteen cubic centimeters, and more desirablyabout seventeen cubic centimeters, and a weight of approximatelytwenty-seven grams.

The pulse generator 18 can deliver a range of stimulation parameters tothe lead 12 and electrode 16, e.g., output current ranges of about 0.1mA to about 20 mA, pulse duration ranges of about 0.1 microseconds toabout 500 microseconds, frequency ranges of about one pulse per secondto about 130 pulses per second, and duty cycle ranges from about zero toabout 100 percent. The delivered stimulus may be an asymmetric biphasicwaveform with zero net DC (direct current).

The implantable pulse generator 18 desirably incorporates circuitryand/or programming to assure that the implantable pulse generator 18 maysuspend stimulation, and perhaps fall-back to only very low ratetelemetry, and eventually suspends all operations when the battery 22has discharged the majority of its capacity (i.e., only a safety margincharge remains). Once in this dormant mode, the implantable pulsegenerator may provide limited communications and may be in condition forreplacement if a primary battery is used, or it must be recharged.

When a rechargeable battery is used, the battery desirably has acapacity of as small as 30 mA-hr and up to about 120 mA-hr or more, andrecharging of the rechargeable battery may be required less than weekly.When the rechargeable battery has only a safety margin charge remaining,it can be recharged in a time period of not more than six hours.

The patient controller 80 may also be belt or clothing worn and used tocharge the rechargeable batteries of the pulse generator 18 as needed.Charging may be achieved via an inductive RF link using a charge coil onor near the skin in close proximity to the IPG. The patient controller80 may also be configured to provide the user with information on pulsegenerator battery status and stimulus levels.

The implantable pulse generator 18 desirably includes a lead connectionheader 14 (see FIGS. 5A to 6B), for connecting the lead(s) 12 that mayenable reliable and easy replacement of the lead/electrode, and includesa small antenna 27 for use with the wireless telemetry feature.

The connection header (top header) 14 may be easy to use, reliable, androbust enough to allow multiple replacements of the implantable pulsegenerator after many years (e.g., more than ten years) of use. Thesurgical complexity of replacing an implantable pulse generator isusually low compared to the surgical complexity of correctly placing theimplantable lead 12/electrode 16 in proximity to the target nerve/tissueand routing the lead 12 to the implantable pulse generator. Accordingly,the lead 12 and electrode 16 desirably has a service life of at leastten years with a probable service life of fifteen years or more. Basedon the clinical application, the implantable pulse generator may nothave this long a service life. The implantable pulse generator servicelife may largely be determined by the power capacity of the Lithium Ionbattery 22, and is likely to be three to ten years, based on the usageof the device. Desirably, the implantable pulse generator 18 has aservice life of at least three years.

As described above, the implantable pulse generator preferably uses alaser welded titanium case. As with other active implantable medicaldevices using this construction, the implantable lead(s) 12 connect tothe implantable pulse generator through a molded or cast polymericconnection header 14. Metal-ceramic or metal-glass feed-thrus maintainthe hermetic seal of the titanium capsule while providing electricalcontact to the electrical contacts of the lead 12/electrode 16.

The standard implantable connectors may be similar in design andconstruction to the low-profile IS-1 connector system (per ISO 5841-3).The IS-1 connectors have been in use since the late 1980s and have beenshown to be reliable and provide easy release and re-connection overseveral implantable pulse generator replacements during the service lifeof a single pacing lead. Full compatibility with the IS-1 standard, andmating with pacemaker leads, is not a requirement for the implantablepulse generator.

The implantable pulse generator connection system may include amodification of the IS-1 connector system, which shrinks the axiallength dimensions while keeping the format and radial dimensions of theIS-1. For application with more than two electrode conductors, the topheader 14 may incorporate one or more connection receptacles each ofwhich accommodate leads with typically four conductors. When two or moreleads are accommodated by the header, these leads may exit theconnection header in opposite directions (i.e., from opposite sides ofthe header), as seen in FIGS. 6A and 6B.

These connectors can be similar to the banded axial connectors used byother multi-polar implantable pulse generators or may follow theguidance of the draft IS-4 implantable connector standard. The design ofthe implantable pulse generator housing and header 14 preferablyincludes provisions for adding the additional feed-thrus and largerheaders for such indications.

The inclusion of the antenna 27 for the wireless telemetry inside theconnection header 14 may be necessary as the shielding offered by thetitanium case may severely limit (effectively eliminate) radio wavepropagation through the case. The antenna 27 connection may be madethrough a feed-thru similar to that used for the electrode connections.Alternatively, the wireless telemetry signal 82 may be coupled insidethe implantable pulse generator onto a stimulus output channel andcoupled to the antenna 27 with passive filtering/couplingelements/methods in the connection header 14.

III. Features of the Lead and Electrode

A. Implantation in Pelvic Region

The lead 12 and electrode 16 are sized and configured to be insertedinto and to rest in the targeted tissue region in the lower pelvicregion without causing pain or discomfort or impact body image.Desirably, the lead 12 and electrode 16 can be inserted using the small(e.g., smaller than 16 gauge) introducer sleeve 32 with minimal tissuetrauma. The lead 12 and electrode 16 are formed from a biocompatible andelectrochemically suitable material and possess no sharp features thatcan irritate tissue during extended use. Furthermore, the lead 12 andelectrode 16 possess mechanical characteristics including mechanicalcompliance (flexibility) along their axis (axially), as well asperpendicular to their axis (radially), and unable to transmit torque,to flexibly respond to dynamic stretching, bending, and crushing forcesthat can be encountered in this body region without damage or breakage,and to accommodate relative movement of the pulse generator coupled tothe lead 12 without imposing force or torque to the electrode 16 whichtends to dislodge the electrode.

Furthermore, one embodiment of a lead 12 and electrode 16 may alsoinclude an anchoring means 70 for providing retention strength to resistmigration within or extrusion from the targeted tissue region inresponse to force conditions normally encountered during periods ofextended use (see FIGS. 8 and 9). In addition, the anchoring means 70 isdesirably sized and configured to permit the electrode 16 position to beadjusted easily during insertion, allowing placement at the optimallocation where unilateral or bilateral stimulation of a target nerve Aand/or a target nerve B occurs. The anchoring means 70 functions to holdthe electrode at the implanted location despite the motion of the tissueand small forces transmitted by the lead due to relative motion of theconnected pulse generator due to changes in body posture or externalforces applied to the abdomen. However, the anchoring means 70 shouldallow reliable release of the electrode 16 at higher force levels, topermit withdrawal of the implanted electrode 16 by purposeful pulling onthe lead 12 at such higher force levels, without breaking or leavingfragments, should removal of the implanted electrode 16 be desired.

B. The Lead

FIGS. 8 to 11 show a representative embodiment of a lead 12 that providethe foregoing features. The implantable lead 12 comprises a molded orextruded component 72, which encapsulates one or more stranded or solidwire elements 74, and includes the connector 62 (shown in FIG. 12). Thewire element may be bifilar, as shown in FIG. 11, and may be constructedof coiled MP35N nickel-cobalt wire or wires that have been coated inpolyurethane. In a representative embodiment with two electricallyconductive surfaces 16 (as described below), one wire element 74 may becoupled to the distal electrode 16 and the pin 62A of the connector 62.A second wire element 74 may be coupled to the proximal electrode 16 andthe ring 62B on the connector 62. The molded or extruded lead 12 canhave an outside diameter ranging between about 0.05 mm to about 5.0 mm,and as small as about one (1) mm, and desirably about 1.9 mm. The lead12 may also include an inner lumen 13 having a diameter about 0.2millimeters to about 0.5 millimeters, and desirably about 0.35millimeters. The lead 12 may be approximately 10 cm to 40 cm in length,although the lead may be shorter or longer, depending on the targetnerve to be stimulated and the anatomy of the patient. The lead 12provides electrical continuity between the connector 62 and theelectrode 16.

The coil's pitch can be constant or, as FIG. 10 shows, the coil's pitchcan alternate from high to low spacing to allow for flexibility in bothcompression and tension. The tight pitch may allow for movement intension, while the open pitch may allow for movement in compression.

A standard IS-1 or similar type connector 62 at the proximal endprovides electrical continuity and mechanical attachment to the pulsegenerator 18. The lead 12 and connector 62 all may include provisions(e.g., lumen 13) for a guidewire that passes through these componentsand the length of the lead 12 to the conductive electrode 16 at thedistal end.

C. The Electrode

The electrode 16 may comprise one or more electrically conductivesurfaces. Two conductive surfaces are show in FIGS. 8 and 9. The twoconductive surfaces can be, used either A) as one two individualstimulating (cathodic) electrodes in a monopolar configuration using themetal case of the pulse generator 18 as the return (anodic) electrode orB) either the distal or proximal conductive surface as a individualstimulating (cathodic) electrode in a monopolar configuration using themetal case of the pule generator 18 as the return (anodic) electrode orC) in bipolar configuration with one electrode functioning as thestimulating (cathodic) electrode and the other as the return (anodic)electrode.

In general, bipolar stimulation is more specific than monopolarstimulation—the area of stimulation is much smaller—which may be good ifthe electrode 16 is close to the target nerve. But if the electrode 16is farther from the target nerve, then a monopolar configuration couldbe used because with the pulse generator 18 acting as the returnelectrode, activation of the nerve may be less sensitive to exactplacement than with a bipolar configuration.

In use, a physician may first attempt to place the electrode 16 close tothe target nerve so that it could be used in a bipolar configuration,but if bipolar stimulation failed to activate the target nerve, then theelectrode 16 could be switched to a monopolar configuration. Twoseparate conductive surfaces on the electrode 16 provide an advantagebecause if one conductive surface fails to activate the target nervebecause it is too far from the nerve, then stimulation with the secondconductive surface could be tried, which might be closer to the targetnerve. Without the second conductive surface, a physician would have toreposition the electrode to try to get closer to the target nerve.

The electrode 16, or electrically conductive surface or surfaces, can beformed from PtIr (platinum-iridium) or, alternatively, 316L stainlesssteel. Each electrode 16 possess a conductive surface of approximately10 mm²-20 mm² and desirably about 16.5 mm². This surface area providescurrent densities up to 2 mA/mm² with per pulse charge densities lessthan about 0.5 μC/mm². These dimensions and materials deliver a chargesafely within the stimulation levels supplied by the pulse generator 18.

Each conductive surface has an axial length in the range of about threeto five millimeters in length and desirably about four millimeters. Whentwo or more conductive surfaces are used, either in the monopolar orbipolar configurations as described, there may be an axial spacingbetween the conductive surfaces in the range of 1.5 to 2.5 millimeters,and desirably about two millimeters.

D. The Anchoring Means

In the illustrated embodiment (see FIGS. 8 and 9), the lead may beanchored by anchoring means 70 specifically designed to secure theelectrode 16 in tissue in electrical proximity to the target nerve, withor without the support of muscle tissue. The anchoring means 70 takesthe form of an array of shovel-like paddles or scallops 76 proximal tothe proximal-most electrode 16 (although a paddle 76 or paddles couldalso be proximal to the distal most electrode 16, or could also bedistal to the distal most electrode 16). The paddles 76 as shown anddescribed are sized and configured so they may not cut or score thesurrounding tissue. It is to be appreciated that anchoring means are nota requirement for the present invention.

The paddles 76 are desirably present relatively large, generally planarsurfaces, and are placed in multiple rows axially along the distalportion of lead 12. The paddles 76 may also be somewhat arcuate as well,or a combination of arcuate and planar surfaces. A row of paddles 76comprises two paddles 76 spaced 180 degrees apart. The paddles 76 mayhave an axial spacing between rows of paddles in the range of six tofourteen millimeters, with the most distal row of paddles 76 adjacent tothe proximal electrode, and each row may be spaced apart 90 degrees. Thepaddles 76 are normally biased toward a radially outward condition intotissue.

In this condition, the large surface area and orientation of the paddles76 allow the lead 12 to resist dislodgement or migration of theelectrode 16 out of the correct location in the surrounding tissue. Inthe illustrated embodiment, the paddles 76 are biased toward aproximal-pointing orientation, to better resist proximal migration ofthe electrode 16 with lead tension. The paddles 76 are desirably madefrom a polymer material, e.g., high durometer silicone, polyurethane, orpolypropylene, bonded to or molded with the lead 12.

The paddles 76 are not stiff, i.e., they are generally pliant, and canbe deflected toward a distal direction in response to exerting a pullingforce on the lead 12 at a threshold axial force level, which may begreater than expected day-to-day axial forces. The paddles 76 are sizedand configured to yield during proximal passage through tissue in resultto such forces, causing minimal tissue trauma, and without breaking orleaving fragments, despite the possible presence of some degree oftissue in-growth. This feature permits the withdrawal of the implantedelectrode 16, if desired, by purposeful pulling on the lead 12 at thehigher axial force level.

Desirably, and as previously described, the anchoring means 70 may beprevented from fully engaging body tissue until after the electrode 16has been deployed. The electrode 16 may not be deployed until after ithas been correctly located during the implantation (installation)process.

More particularly, and as previously described, the lead 12 andelectrode 16 are intended to be percutaneously introduced through thesleeve 32 shown in FIG. 12. As shown, the paddles 76 assume a collapsedcondition against the lead 12 body when within the sleeve 32. In thiscondition, the paddles 76 are shielded from contact with tissue. Oncethe location is found, the sleeve 32 can be withdrawn, holding the lead12 and electrode 16 stationary. Free of the sleeve 32, the paddles 76spring open to assume their radially deployed condition in tissue,fixing the electrode 16 in the desired location. In the radiallydeployed condition, the paddles have a diameter (fully opened) of aboutfour millimeters to about six millimeters, and desirably about 4.8millimeters.

The lead has two ink markings 54, 55 to aid the physician in its properplacement. The most distal marking 20 (about 11 cm from the tip) alignswith the external edge of the introducer sleeve 32 when the tip of thelead is at the tip of the sleeve 32. The more proximal marking 21 (about13 cm from the tip) aligns with the external edge of the sleeve 32 whenthe introducer has been retracted far enough to expose the tines 76. Acentral lumen 13 allows for guidewire 94 insertion and removal tofacilitate lead placement. A funnel 95 may be included to aid ininserting the guidewire 94 into the lumen 13 in the lead 12.

The anchoring means 70 may be positioned about 10 millimeters from thedistal tip of the lead, and when a second anchoring means 70 is used,the second anchoring means 70 may be about 20 millimeters from thedistal tip of the lead.

The position of the electrode 16 relative to the anchoring means 70, andthe use of the sleeve 32, allows for both advancement and retraction ofthe electrode delivery sleeve 32 during implantation whilesimultaneously delivering test stimulation. The sleeve 32 can be drawnback relative to the lead 12 to deploy the anchoring means 70, but onlywhen the physician determines that the desired electrode location hasbeen reached. The withdrawal of the sleeve 32 from the lead 12 causesthe anchoring means 70 to deploy without changing the position ofelectrode 16 in the desired location (or allowing only a small andpredictable, set motion of the electrode 16). Once the sleeve 32 isremoved, the flexible, silicone-coated or polyurethane-coated lead 12and electrode 16 are left implanted in the tissue.

IV. Implantation Methodology

There are at least three alternative methods for placing one or morelead/electrode(s) near one or more target nerves, and each are describedbelow. The patient may undergo monitored anesthesia care (MAC), which isa planned procedure during which the patient undergoes local anesthesiatogether with sedation and analgesia. During MAC, the patient is sedatedand amnestic but always remains responsive when stimulated to do so.Local anesthesia—e.g., 1% Lidocaine (2-5 ccs) or equivalent—may beinjected prior to making the anticipated lead 12 incision site 60. Thepatient preparation may be the same for all implantation methods.Although the lateral views show the male anatomy, similar approaches mayalso be used in the female.

A. Anterior Approach

Referring the FIGS. 13 and 14, the site for the lead insertion 60 isdesirably located midline or near-midline, over the pubic symphysisaiming toward the clitoris (or the base of the penis in males).

Once local anesthesia is established, a needle/introducer may beadvanced percutaneously into the anesthetized site 60 to a depth ofabout five centimeters to about seven centimeters necessary to reach thetarget site between the pubic symphysis and the clitoris in females, orthe base of the penis in males, to stimulate a target nerve(s) (e.g.,dorsal genital nerves). The needle/introducer may then be replaced witha lead 12 threaded through the initially inserted sheath or needle. Itis to be appreciated that this approximate insertion depth may varydepending on the particular anatomy of the patient. The physician mayuse one hand to guide the lead 12 and the other hand to hold surroundingtissue to stabilize the area. Once the lead 12 is positioned, it may becoupled to a test stimulator to apply stimulation waveforms through thelead 12 and electrode 16 concurrent with positioning of the electrode 16to confirm the desired location.

B. Perineal Approach

Referring to FIGS. 15 and 16, the site for the lead insertion 60 may beperpendicular to the skin into the anesthetized site 60 located behindthe scrotum as shown or lateral to the scrotum or near the base of thepenis (e.g., lateral or posterior to the penis base). A similar approachmay also be used in the female.

Once local anesthesia is established, a needle/introducer may beadvanced percutaneously into the anesthetized site 60 to a target depthnecessary to reach the target site along the urethra to stimulate atarget nerve(s) (e.g., urethral afferents). The needle/introducer maythen be replaced with a lead 12 threaded through the initially insertedsheath or needle. It is to be appreciated that insertion depths may varydepending the particular anatomy of the patient. The physician may useone hand to guide the lead 12 and the other hand to hold surroundingtissue to stabilize the area. Once the lead 12 is positioned, it may beagain coupled to a test stimulator to apply stimulation waveformsthrough the lead 12 and electrode 16 concurrent with positioning of theelectrode 16 to confirm the desired location.

C. Posterior Approach

The user may be placed in a lateral decubitus position with their back,hips and legs flexed. Referring the FIGS. 17 and 18, the site for thelead insertion 60 may be approximately 2 cm lateral and 2 cm caudal tothe midpoint of a line defined between the posterior superior iliacspine and the ischical tuberosity.

Once local anesthesia is established, a needle/introducer may beadvanced percutaneously into the anesthetized site 60 to a target depthnecessary to reach the target site (e.g., at, along side of, and/or nearAlcock's canal) to stimulate a target nerve(s) (e.g., pudendal nerves).The proximity of the needle tip to the pudendal nerve may be minimizedthrough successively finer adjustments of the stimulus amplitude (e.g.,an initial current of 3 mA, a pulse width of 0.1 sec. and a frequency of2 Hz, for example), and electrode tip position, until external analsphincter twitches can be evoked with stimuli less than 1 mA, forexample. The needle/introducer may then be replaced with a lead 12threaded through the initially inserted sheath or needle. It is to beappreciated that insertion depths may vary depending on the particularanatomy of the patient. The physician may use one hand to guide the lead12 and the other hand to hold surrounding tissue to stabilize the area.Once the lead 12 is positioned, it may be again coupled to a teststimulator to apply stimulation waveforms through the lead 12 andelectrode 16 concurrent with positioning of the electrode 16 to confirmthe desired location.

V. Stimulating Catheter

A stimulating catheter 150 may be used as a clinical screening tool toidentify appropriate candidates for the bladder function restorationsystem (see FIGS. 20A through 23). If a subject's stimulating cathetertest demonstrates that urethral stimulation may be able to empty thebladder, then a fine wire lead known in the art (or a lead 12 as shownand described) would be implanted near the urethra in close proximity tothe urethral afferents using one of the described approaches. Similarly,another fine wire lead (or a lead 12 as shown and described) may beplaced near the dorsal genital nerve. After implantation of one or moreleads, the subject would be sent home for a predetermined test period(e.g., a week) with the percutaneous leads connected to an externalpulse generator (not shown).

For this test period, an external pulse generator can be used of thetype described in U.S. Pat. No. 7,120,499, issued Oct. 10, 2006, andentitled “Portable Percutaneous Assemblies, Systems, and Methods forProviding Highly Selective Functional or Therapeutic Neurostimulation,”which is incorporated herein by reference. Optionally, an external pulsegenerator can be used of the type described in co-pending U.S. patentapplication Ser. No. 11/595,556, filed Nov. 10, 2006, and entitled“Portable Assemblies, Systems, and Methods for Providing Functional orTherapeutic Neurostimulation,” which is also incorporated herein byreference.

If the home trial provides functional results, e.g., prevents thepatient from leaking between voids, and achieves a residual post-voidbladder volume of a predetermined amount (e.g., less than 50 ml), thenthe patient may proceed to receive a fully implanted system, includingan implantable pulse generator (IPG) to evaluate continence and emptyingin the home environment over a longer period (e.g., 3 to 6 months). Incontrast to the implantation of the VOCARE system on the sacral spinalroots which requires a time consuming and invasive laminectomy, thepresent systems and methods may allow urologists to place thelead/electrode(s) near the target nerve(s) easily and reliably becausethe urethra and genitals are an area in which urologists are comfortableand familiar.

During the first period of stimulation, the subjects may be in“continence mode” as their bladder fills, using dorsal genital nervestimulation via a first lead to remain dry. When they are ready tourinate, they may press a button on their external controller to switchinto “micturition mode” to empty their bladder with urethral afferentstimulation via a second lead. When they are finished urinating, theymay press the other button on the external stimulator to switch backinto “continence mode.”

The idea of stimulating the urethra is known, but the stimulatingcatheter 150 provides a unique combination of features. The stimulatingcatheter 150 is adapted to be used to measure bladder pressures andstimulate the urethra at the same time. Previously, bladder pressure wasmeasured with one catheter, and another catheter-like lead, similar to adeep brain stimulation lead, which was placed alongside it to providethe stimulation. This arrangement is cumbersome for clinicians andprovides less accurate information about the location of stimulationbecause the stimulating lead can move relative to the urethra.

As can be seen in FIG. 20A, the novel stimulating catheter 150 has aballoon 152 that may be inflated in the bladder neck that secures thecatheter and one or more stimulating electrodes 154 in place so it doesnot move within the urethra. The stimulating catheter 150 as shown hasmultiple electrodes 154 along its length (e.g., 17 electrodes are shown)that can stimulate the urethra. This means once the catheter 150 is inplace, it does not have to be moved again until it is removed. This is acrucial feature because movement inside the urethra can activateurethral afferents, which are the very fibers that need to be screened.Thus, movement of the stimulating catheter 150 along the urethra canconfound the screening and also lead to unwanted elicitation of reflexessuch as a reflex bladder spasm or contraction.

Multiple stimulating electrodes 154 placed along the catheter body 160allow the stimulating catheter 150 to be able to stimulate differentportions of the urethra without having to move the catheter inside theurethra once the catheter 150 is in place. Each electrode 154 may besecured to the catheter body with an adhesive 155 (see FIG. 20B), whichalso serves to provide a smooth transition from the catheter body 160 toan edge of an electrode 154. The electrodes 154 near the proximalportion 162 of the catheter body 160 are generally spaced about 1.0 cmto 2.0 cm apart, and more desirably about 1.5 cm apart, and theelectrodes 154 near the distal portion 164 are generally spaced about0.1 cm to 1.0 cm apart, and more desirably about 0.5 cm apart.

FIG. 20C shows an alternative configuration of electrodes 154. More thanone configuration provides for flexibility depending on the patientsanatomy. In FIG. 20C, fifteen electrodes 154 are shown. The electrodes154 near the proximal portion 162 of the catheter body 160 are generallyspaced about 1.0 cm to 2.0 cm apart, and more desirably about 1.5 cmapart, and the electrodes 154 near the distal portion 164 are generallyspaced about 0.1 cm to 1.0 cm apart, and more desirably about 0.5 cmapart. An electrode free gap 156 may be provided between the higherconcentration of electrodes near the distal portion 164 and theelectrodes near the proximal portion 162. The gap 156 may be about 5 cmto 7 cm, and more desirably about 6 cm.

The multiple electrodes 154 are adapted to enable urethral stimulationto elicit bilateral activation of the urethral afferents. The multipleelectrodes permit bipolar stimulation and ensure that one electrode maybe located within a short distance (e.g. one cm or less) of the portionof the urethra most sensitive to electrical stimulation. Animal studieshave shown the caudal urethra to be the most sensitive becauseelectrical stimulation of the caudal urethra evoked the largest compoundnerve action potentials in urethral afferents and sustained bladdercontractions most consistently with the lowest stimulation amplitudescompared to other urethral locations.

The stimulating catheter 150 may also be used in both men and women. Thehigher concentration of electrodes 154 near the distal portion 164 ofthe catheter body 160 serves to most effectively stimulate the shorterurethra in women (generally about two to four cm long), and a largenumber of electrodes 154 along the length of the catheter body 160 aredesigned to accommodate urethras of longer lengths, and the higherconcentration of electrodes 154 may be placed to stimulate the most wellinnervated portions of the urethra in either a man or a woman.

The balloon 152 may also be wedge shaped which may help prevent leakagearound the balloon and may allow iso-volumetric measurements. Thisfeature allows the stimulating catheter 150 to be used to analyzebladder contractions at the same volume without having to re-fill thebladder after each bladder contraction. This may be beneficial for atleast two reasons: 1) it takes time to fill the bladder, and in order tomake the procedure of analyzing responses to urethral stimulation apractical out-patient procedure, the total time needs to be kept down toabout one to two hours, and having to re-fill the bladder after eachbladder contraction would take too long (e.g., more than two hours), and2) it makes the screening more robust and the results simpler and easierto analyze because the bladder reflexes are time and, history dependent.This means that every fill has an effect on each of the followingbladder contractions, meaning that evoking bladder contractions andfilling between bladder contractions to replace the leaked volume is notthe same as evoking iso-volumetric bladder contractions without fillingbetween each contraction.

Additionally, the stimulating catheter has a coude (curved) tip 158which enables it to be inserted in men with enlarged prostates (see FIG.20A). Without the curved tip 158, it would be nearly impossible to placethe stimulating catheter in most men with enlarged prostates. Thestimulating catheter body 160 may be small in diameter (e.g., twelveFr), meaning that after the balloon 152 is deflated in the bladder neck,the rest of the catheter body 160 may not obstruct the urethra and mayallow for voiding (around the catheter body) to be monitored.

The catheter body 160 is desirably a dual lumen body having a proximalportion 162 and a distal portion 164. The first lumen 166 extends from afitting 168 near the proximal end 162 to the balloon 152 near the distalend 164, and carries an insulated solid or stranded wire element 170 foreach electrode 154 (see FIGS. 21 and 22). The first lumen 166 alsoserves as a path for fluid flow (i.e., saline or distilled water) tofill and drain the balloon 152. The fitting 168 may be adapted to beconnected to a fluid pump. Alternatively, a third lumen may be providedto serve as the balloon fill lumen.

The wire elements 170 for each electrode 154 are carried in an extension176 which extends from the first lumen 166 to a connector 178. Theconnector 178 then couples to a computer system or external pulsegenerator, for example, to provide selective stimulation to the multipleelectrodes 154.

The second lumen 172 extends from a fitting 174 near the proximal end162 to an opening 176 near the catheter body tip 158, and serves as apath for fluid flow to fill the bladder, and to measure fluid pressure.The fitting 174 may be adapted to be connected to a fluid pump andpressure transducer. The bladder is typically filled with a salinesolution, and the solution may contain a contrast medium to allowviewing of the bladder filling using fluoroscopy.

VI. Representative Indications

Due to its technical features, the implant system 10 can be used toprovide beneficial results in diverse therapeutic and functionalrestorations indications.

For example, in the field of urology or urologic dysfunctions, possibleindications for use of the implant system includes the treatment of (i)urinary and fecal incontinence; (ii) micturition/retention; (iii)restoration of sexual function; (iv) defecation/constipation; (v) pelvicfloor muscle activity; and/or (vi) pelvic pain.

The foregoing is considered as illustrative only of the principles ofthe invention. Furthermore, since numerous modifications and changeswill readily occur to those skilled in the art, it is not desired tolimit the invention to the exact construction and operation shown anddescribed. While the preferred embodiment has been described, thedetails may be changed without departing from the invention.

1.-48. (canceled)
 49. A method of providing bladder function comprising: providing a first lead including one or more stimulation electrodes, providing a second lead including one or more stimulation electrodes, positioning the first lead on, in, or near a dorsal genital nerve, positioning the second lead on in, or near urethral afferents, applying a stimulation pulse to the first lead and to the second lead to provide bladder function.
 50. A method according to claim 49: wherein positioning the first lead comprises: inserting the first lead midline or near midline over the pubic symphysis aiming toward the clitoris in females or base of penis in males, and advancing the first lead to reach the dorsal genital nerve between the pubic symphysis and the clitoris in females or the base of the penis in males.
 51. A method according to claim 49: wherein positioning the second lead comprises: inserting the second lead through the skin of the perineum, advancing the second lead to a target depth necessary for positioning along the urethra.
 52. A method of improving bladder function comprising: providing a first elongated lead comprising one or more stimulation electrodes sized and configured to be implanted in a tissue region at or near a target A, providing a second elongated lead comprising one or more stimulation electrodes sized and configured to be implanted in a tissue region at or near a target B, providing a pulse generator to convey one or more electrical stimulation waveforms to the first lead to stimulate the target A and to the second lead to stimulate the target B, implanting the first lead in the tissue region at or near the target A, implanting the second lead in the tissue region at or near the target B, coupling the first lead and the second lead to the pulse generator, operating the pulse generator to convey one or more electrical stimulation waveforms to the first lead to stimulate the target A, the stimulation waveforms conveyed to the stimulation electrodes affecting afferent stimulation of target A, operating the pulse generator to convey one or more electrical stimulation waveforms to the second lead to stimulate the target B, the stimulation waveforms conveyed to the stimulation electrodes affecting afferent stimulation of target B, and the afferent stimulation activating central nervous system circuitry that coordinates and/or produces efferent activity in target A and/or efferent activity in target B to produce and/or further continence and/or bladder emptying.
 53. A method of improving bladder function comprising: providing an elongated lead comprising one or more stimulation electrodes sized and configured to be implanted in a tissue region at or near a target A and/or a target B, providing a pulse generator to convey one or more electrical stimulation waveforms to the elongated lead to stimulate the target A and/or the target B, implanting the elongated lead in the tissue region at or near the target A and/or the target B, coupling the elongated lead to the pulse generator, operating the pulse generator to convey one or more electrical stimulation waveforms to the elongated lead to stimulate the target A and/or the target B, the stimulation waveforms conveyed to the stimulation electrodes affecting afferent stimulation of target A and/or target B, the afferent stimulation activating central nervous system circuitry that coordinates and/or produces efferent activity in target A and/or efferent activity in target B to produce and/or further continence and/or bladder emptying.
 54. A method according to claim 53: wherein the afferent stimulation activating central nervous system circuitry that coordinates and/or produces efferent activity in target A and/or efferent activity in target B and/or the pelvic nerve (s) and/or hypogastric nerve (s) to produce and/or further continence and/or bladder emptying.
 55. A method according to claim 53: wherein implanting the elongated lead comprises: inserting the lead midline or near midline over the pubic symphysis aiming toward the clitoris in females or base of penis in males, and advancing the lead to reach the target A and/or target B between the pubic symphysis and the clitoris in females or the base of the penis in males.
 56. A method according to claim 53: wherein implanting the elongated lead comprises: inserting the elongated lead through the skin of the perineum, and advancing the lead to a target depth necessary to reach the target A and/or target B along the urethra.
 57. A method according to claim 53: wherein implanting the elongated lead comprises: inserting the lead about 2 cm lateral and about 2 cm caudal to the midpoint of a line defined between the posterior superior iliac spine and the ischical tuberosity, and advancing the lead to a target depth necessary to reach the target A and/or the target B.
 58. A method of restoring bladder function comprising: implanting a first lead adapted for dorsal genital nerve stimulation, implanting a second lead adapted for urethral afferent stimulation, coupling the first lead to a pulse generator, coupling the second lead to the pulse generator, operating the pulse generator in a continence mode to allow the bladder to fill, and after the bladder has filled to a level, operating the pulse generator in a micturition mode to empty some or all of the contents of the bladder.
 59. A system for restoring bladder function comprising: a first lead adapted for dorsal genital nerve stimulation, a second lead adapted for urethral afferent stimulation, a pulse generator adapted to couple to the first lead and the second lead to provide electrical stimulation to the dorsal genital nerve and the urethral afferents, the pulse generator including a continence mode to allow the bladder to fill, and the pulse generator including a micturition mode to empty some or all of the contents of the bladder after the bladder has filled to a level. 